Direction-selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction, and are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene. The preferred direction of direction-selective ganglion cells cluster along the cardinal directions (up, down, left and right) and the direction-selective ganglion cells sensitive to each cardinal direction are organized into mosaics such that at each point in space, each direction of motion is represented. The predominant model for the generation of direction selectivity in the retina is that a particular class of interneurons forms inhibitory synapses on the null side of the dendritic tree of direction- selective ganglion cells. The mechanisms that instruct the emergence of mosaics comprised of cells that receive an asymmetric distribution of inhibitory inputs during development are unknown. Here we propose to use a combination of state-of-the-art electrophysiological and imaging techniques to determine the mechanisms that underlie the development of these two essential features of direction-selectivity - the circuits that underlie the null side inhibition and the existence of direction-selective ganglion cells mosaics. In particular, we will determine whether spontaneous retinal activity plays a critical role in the formation of these circuits. PUBLIC HEALTH RELEVANCE: Our research goal is to determine the factors that instruct the development of visual responses in the mammalian retina. In particular, we are studying the circuits that underlie the ability of the retina to detect the direction of motion of an object in the visual scene. This "direction-selectivity" is critical for the normal visually-driven reflexes that stabilize an image on the retina as we move through a visual scene. Our work will determine what role neural activity in the retina plays in the wiring up of these direction-selective circuits. Developing a detailed understanding of the organizing principles that govern the normal development of the circuits may make it possible to understand the origin of neurological birth defects. Very early in the development, before visual experience is possible, both electrical and chemical activity is generated spontaneously throughout the immature visual system. There is growing evidence that this early activity is critical for the appropriate development of circuits that mediate vision. These findings give us insights as to why exposure of fetuses to pharmacological agents can lead to a variety of neuropathologies. In addition, gaining insights into the role of neural activity will provide critical insights into devising strategies that allow the nervous system to rewire normal functioning neural circuits in response to developmental abnormalities that affect vision.